tbuckley/cabot-search huggingface dataset:
POS0619 CLINICAL AND SUBCLINICAL INTERSTITIAL LUNG DISEASE IN RHEUMATOID ARTHRITIS: ASSOCIATED FACTORS.
Authors: M. Rojas-Giménez, J. Calvo Gutierrez, R. Ortega Castro, M. L. Ladehesa Pineda, A. Escudero Contreras
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To evaluate the differences between patients with rheumatoid arthritis (RA) with and without interstitial lung disease (ILD), to identify factors associated with the development of ILD and to evaluate subclinical ILD; prevalence and factors associated with its development. Methods Observational and cross-sectional study of a cohort of patients with RA (ACR/EULAR 2010) and with ILD and a control group of patients without ILD. Both groups with HRCT performed in the last 18 months. The date of the last HRCT was considered as the study date. The % of patients who had subclinical ILD was retrospectively evaluated, defining this as pulmonary involvement due to a requested HRCT without any previous respiratory symptoms. Demographic variables, activity data (DAS28VSG, SDAI and CDAI on the study date), RF and ACPA levels, RA severity data and treatments they were receiving were collected. Descriptive analysis, χ 2 or t-Student and multivariate logistic regression analysis was performed to find predictive variables of the development of ILD. Results 66 patients with RA (41 with ILD and 25 without ILD) were included. The main differences between both groups are shown in Table 1. In the group of patients with ILD, the male sex predominated, they were older, with a longer duration of the disease and a longer diagnostic delay of RA. They made more use of biological therapies with better control of the disease by DAS28, SDAI and CDAI. Pulmonary function preserved by respiratory function tests. Of the total number of patients with ILD, 15 (36.6%) did not present any respiratory symptoms when the HRCT was requested. The reasons for their request were: finding abnormalities on chest X-ray (66.7%) and dry crackles on examination (33.3%). Subclinical ILDs were diagnosed with less evolution time of RA than clinical ones. In the rest of the variables there were no differences with the clinical ILD. The variables independently associated with the development of ILD, adjusted for age, tobacco use and ACPA at high titers, were male sex [OR = 4.2 (95% CI 1.05-19.7), p = 0.049] and time of evolution of RA [OR = 1.08 (95% CI 1.02-1.17), p = 0.014]. Conclusion In our cohort, the prevalence of subclinical ILD was high (36%). Clinical characteristics, disease activity and ILD data (PFT and HRCT patterns) were similar between clinical and subclinical ILD, but prospective studies are needed to assess whether the course and prognosis in both groups is also similar. Bearing in mind that ILD is an important cause of death in our patients, we must actively search for this condition in order to treat it early and improve its prognosis. Disclosure of Interests None declared
AB0294 VITAMIN D LEVEL AND LOCOMOTIVE FUNCTIONS IN WOMEN WITH RHEUMATOID ARTHRITIS
Authors: N. Toroptsova, O. Dobrovolskaya, A. Sorokina, O. Nikitinskaya, E. Samarkina, M. Cherkasova
Journal: Annals of the Rheumatic Diseases (2022)

Background Muscle health is an important aspect of rheumatoid arthritis (RA). A decrease in muscle mass and physical performance is a frequent complication of RA that contributes to inability to work and reduced quality of life. Vitamin D deficiency is also common in these patients. Objectives To assess the relationship between vitamin D level, muscle strength and physical performance in RA patients. Methods 135 women (mean age 58.5±8.9) with confirmed RA according to ACR/EULAR criteria (2010) were enrolled in the study. Muscle strength of upper extremities was measured using a mechanical dynamometer, of lower extremities – using “Chair stand test” (CST) – assessment of the ability to rise from a chair and sit back down 5 times. Handgrip strength 16 kg and less or CST for more than 15 seconds were the criteria for low muscle strength. All patients underwent “Gate speed test” (GST) and “Timed Up and Go test” (TUG) to assess the physical performance. Serum level 25 (OH)D was performed using the Cobas E411 immunochemiluminescence analyzer and Elecsys Vitamin D total kit, Roche. Results Median 25(OH)D level was 23.7 [18.2; 30.7] ng/ml in RA women with minimum 7.9 ng/ml and maximum 70.0 ng/ml. Insufficiency and deficiency of vitamin D were detected in 56 (41,5%) and 42 (31,1%) women, respectively, with median level 24.1 [21.8; 26.6] ng/ml in the patients with insufficiency and 15.6 [13.6; 17.9] ng/ml – in deficiency group. Vitamin D level was compared between patients with low muscle strength and/or physical performance and women with normal locomotive functions (Table 1). 25(OH)D level was significantly higher in RA women with normal CST and GST &gt;0,8 m/s than in patients with the worst results of these tests. At the same time, we didn’t find differences in handgrip strength and TUG depending on vitamin D level. Table 1. 25(ОН)D in women with RA according to locomotive functions Test 25(ОН)D р CST ≤15 seconds 26,7 [20,4; 32,2] 0,036 &gt;15 seconds 21,0 [17,9; 25,1] GST &gt;0,8 m/s 26,1 [19,6; 32,0] 0,043 ≤0,8 m/s 21,1 [17,0; 26,8] Handgrip strength ≥16 kg 23,8 [17,8; 30,2] &gt;0,05 &lt;16 kg 27,7 [19,5; 32,2] TUG &lt;20 seconds 23,7 [17,9; 30,1] &gt;0,05 ≥20 seconds 18,8 [18,1; 21,0] Conclusion The frequency of low vitamin D level was 72,6% in women with RA including deficiency in 31,1% patients. Patients with reduced lower limb strength and low walking speed had significantly lower vitamin D levels, but there were no differences in 25(OH)D and other tests (handgrip strength and TUG). Disclosure of Interests None declared
Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome
Authors: Breno S. Diniz, Benoit H. Mulsant, Charles F. Reynolds, Daniel M. Blumberger, Jordan F. Karp, Meryl A. Butters, Ana Paula Mendes-Silva, Erica L. Vieira, George Tseng, Eric J. Lenze
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. <h3>Objective</h3> To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults. <h3>Design, Setting, and Participants</h3> A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the<i>Diagnostic and Statistical Manual of Mental Disorders</i>(Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021. <h3>Exposure</h3> Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks. <h3>Main Outcomes and Measures</h3> The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples. <h3>Results</h3> There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35;<i>P</i> = .006). In contrast, no individual SASP factors were associated with remission in LLD. <h3>Conclusions and Relevance</h3> Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00892047
Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets
Authors: Léo Laoubi, Morgane Lacoffrette, Séverine Valsesia, Vanina Lenief, Aurélie Guironnet-Paquet, Amandine Mosnier, Gwendoline Dubois, Anna Cartier, Laurine Monti, Jacqueline Marvel, Eric Espinosa, Bernard Malissen, Sandrine Henri, Lucie Mondoulet, Hugh A. Sampson, Audrey Nosbaum, Jean-François Nicolas, Vincent Dioszeghy, Marc Vocanson
Journal: Journal of Allergy and Clinical Immunology (2022)
Superior therapeutic activity of TGF-β-induced extracellular vesicles against interstitial cystitis
Authors: Kwonwoo Song, Ahmed Abdal Dayem, Soobin Lee, Yujin Choi, Kyung Min Lim, Sehee Kim, Jongyub An, Yeokyung Shin, Hyojin Park, Tak-Il Jeon, Soo Bin Jang, Hanbit Bong, Jeong Ik Lee, Geun-Ho Kang, Sejong Kim, Aram Kim, Ssang-Goo Cho
Journal: Journal of Controlled Release (2022)
PB2287: END OF LIFE TRANSFUSIONS IN PATIENTS WITH AN ONCOLOGICAL DIAGNOSIS
Authors: L. Duque, A. P. Brome Uribe, C. Durango Sánchez, V. Vasquez Estrada, L. M. Martínez Sánchez, A. Morales Montoya, J. F. Vargas Silva, L. Herrera Almanza, M. Fonseca Gúzman, M. Saavedra Valencia, S. M. Molina Naranjo
Journal: HemaSphere (2022)

Background: Cancer patients in terminal stages present symptoms related to anemia, other cytopenias and coagulopathies that deteriorate the quality of life. These symptoms can be multicausal and do not improve in most cases with a single medical intervention. Cancer patients in terminal stages present symptoms related to anemia, other cytopenias and coagulopathies that deteriorate the quality of life.1,2 These symptoms can be multicausal and do not improve in most cases with a single medical intervention. Aims: To describe the use of blood transfusions in the 6 months prior to death as a palliative measure, in patients with an oncological diagnosis in the city of Medellin during the period 2013-2018. Methods: Retrospective cohort, in patients with cancer diagnosis who received transfusions in the last 6 months of life, a non-probabilistic sampling of consecutive cases was performed. The analysis executed in SPSS, they were estimated; absolute and relative frequencies and median with interquartile ranges. Results: Out of 3,254 medical records of cancer patients, 151 were included, of which 78 (51.7%) were male, with a median age of 64 years (IQR 52-75). The time to oncological diagnosis had a median of 2 years (IQR 1 and 3). Of the patients included in the study, 62.3% (94) had outpatient management and 37.7% (57) were hospitalized. Palliative treatment with blood products was used in the study patients during the 6 months prior to their death, with a median of 261.5 cubic centimeters (cc) (IQR 242 - 293) of doses of blood products and a median of 1 unit (IQR 1-2) transfused per patient. Summary/Conclusion: The findings of this research allow to appreciate the current panorama in the institutions in which palliative care medical services are provided and the considerations taken into account when transfusing blood products to a patient at the end of life as a therapeutic measure in the context of a human being cared for by professionals specialized in palliative care.
Diagnostic Efficiency of Various Systems for Automatic Analysis of Radiographs in the Detection of Lung Nodule
Authors: U. A. Smolnikova, P. V. Gavrilov, P. K. Yаblonskiy
Journal: Radiology - Practice (2022)

The purpose of the study was to compare the effectiveness of various artificial intelligence systems for detecting foci and rounded lesions in the lungs. For testing, we selected four software products based on convolutional neural networks, positioning themselves as a sensitive system for evaluating digital chest radiographs. An analytical validation method was used for clinical evaluation. For diagnostics, 3 data samples were formed with the identification of signs of diseases (sample 1–5150 radiographs, detection of pathological changes 3 %; sample 2–100 radiographs, detection of pathological changes 6 %; sample 3–300 radiographs, detection of the prevalence of pathological changes 50 %). None of the software products passed the AUC threshold of 0.811 on all three samples. In all three samples, all software products have high accuracy and high sensitivity in detecting round formations, which leads to rare cases of overdiagnosis and special cases of underdiagnosis. The use of digital X-ray image analysis systems based on artificial intelligence technologies is a promising direction for high-quality diagnostics, primarily when considering their young radiologists as an additional opinion.
P1412: UNCOUPLING INK4 PROTEINS FROM CDK4/CDK6 IN HEMATOPOIETIC STEM CELLS
Authors: A. Schirripa, M. Prchal-Murphy, R. Grausenburger, K. Kollmann, V. Sexl
Journal: HemaSphere (2022)

Background: Cell-cycle progression is governed by regulatory proteins including cyclin-dependent kinases (CDKs), cyclins and CDK inhibitors. The INK4 family comprises p16INK4a, p15INK4b, p18INK4c and p19INK4d which are CDK4/6 specific inhibitors. Different tumor types display deletion, mutation, or promoter hypermethylation of the INK4 proteins resulting in enhanced CDK4/6 activity. The INK4a-ARF-INK4b locus encodes for p16INK4a and p15INK4b and for the tumor suppressor protein p14ARF (p19ARF in the mouse) and is one of the most frequently mutated or epigenetically silenced site in human malignancies. CDK4R24C/CDK6R31C double knock-in mice, where R24C and R31C mutations make CDK4/6 fully insensitive to INK4 mediated inhibition, show a shortened survival caused by the onset of a variety of tumors including hematopoietic malignancies. This shows the vital importance of a tight controlled inhibition of CDK4/6 activity in hematopoiesis. Aims: We here explore the consequences of INK4 inhibitory loss on CDK4/6 on the hematopoietic stem cell (HSC) compartment using CDK4R24C/CDK6R31C mice. We propose that INK factors regulate important functions in HSCs by direct binding to CDK4/6. This knowledge is required to understand how to best employ CDK inhibitors in therapeutic settings. Methods: We analyzed the composition of the hematopoietic compartment of CDK4R24C/CDK6R31C double knock-in mice under homeostatic conditions. Long-term self-renewal capacity of CDK4R24C/CDK6R31C bone marrow (BM) cells was assessed by serial bone marrow transplantation (BMT). RNAseq was used to investigate the molecular mechanisms underlying the improved self-renewal of CDK4R24C/CDK6R31C HSCs. Using the stem/progenitor cell line HPCLSK enabled us to perform ChIP qPCR to understand the involvement of CDK4R24C/CDK6R31C for Id1 transcriptional regulation. Results: Upon inhibition of CDK4/6 binding to INK4 proteins, HSC numbers in the BM of CDK4R24C/CDK6R31C mice were reduced. Despite the cell number reduction, CDK4R24C/CDK6R31C HSCs displayed an enhanced self-renewal potential during serial BMT. Transcriptome analysis pointed to the involvement of Id1 in enhanced self-renewal. We indeed found Id1 down-regulated in CDK4R24C/CDK6R31C HSCs at the 3rd round of BMT. CDK6 ChIP experiments confirmed that INK4 binding alters binding of CDK6 to the Id1 promoter, which is significantly reduced in CDK6R31C cells. Summary/Conclusion: Despite reduced qHSCs/MPP1 content under homeostatic conditions, CDK4R24C/CDK6R31C HSCs possess an enhanced self-renewal potential elucidated in serial BMT. We propose that a reduced Id1 expression in qHSCs/MPP1 CDK4R24C/CDK6R31C cells explains this phenotype and underlines improved repopulation ability of CDK4R24C/CDK6R31C BM cells. Our data indicate that INK4 binding to CDK6 dictates its function in regulating transcription.
Systematic pan-cancer analysis of mutation–treatment interactions using large real-world clinicogenomics data
Authors: Ruishan Liu, Shemra Rizzo, Sarah Waliany, Marius Rene Garmhausen, Navdeep Pal, Zhi Huang, Nayan Chaudhary, Lisa Wang, Chris Harbron, Joel Neal, Ryan Copping, James Zou
Journal: Nature Medicine (2022)
Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx
Authors: Juan Carlos Cardet, Kartik Shenoy, Ahmet Baydur, Jennifer K. Carroll, Juan Carlos Celedón, Jing Cui, Prajwal Dara, Brianna Ericson, Victoria E. Forth, Maureen Fagan, Anne L. Fuhlbrigge, Rohit Gupta, Mary K. Hart, Michelle L. Hernandez, Paulina Arias Hernandez, Jean Kruse, Nancy E. Maher, Brian K. Manning, Victor M. Pinto-Plata, Janet Robles, Jacqueline Rodriguez-Louis, Joel B. Shields, Bonnie S. Telon Sosa, Michael E. Wechsler, Elliot Israel
Journal: Journal of Allergy and Clinical Immunology (2022)
PB1841: A NEW APPROACH IN ACUTE MYELOID LEUKEMIA (AML): SAMATYA-PREDICTING SCORE
Authors: I. Serin, B. ORHAN, D. SONMEZ, T. A. CINLI, H. GOZE, H. SERIN, O. YOKUS
Journal: HemaSphere (2022)

Background: Since it is not possible to access all methods simultaneously in determination of prognosis, it is important to use different methods together in acute myeloid leukemia (AML). Aims: We aimed to examine the efficiency for prediction of prognosis and response to induction therapy in non-APL AML cases of the “Samatya-predicting score” that we developed using clinical, cytogenetic and flow cytometric features Methods: A total of 213 patients diagnosed between January 2010-December 2020 were examined. Mortality and response to induction therapy (complete, incomplete, failure) were recorded. The subgroups were formed as follows: Responder: Complete response (CR); non-responder: Incomplete or failure. Patients who were not eligible for the study were excluded. Results: Of the 158 patients included in the study, the median value of risk score was determined as 2,5. The area under the curve for the median risk score of 2,5 in ROC analysis was 0,635 (0,541-0,729; 95% confidence interval, p=0,006) for exitus; while it was 0,605 (0,517-0,692; p=0,024) for being responder. The sensitivity for mortality was 88%, the specificity 42%, the positive predictive value (PPV) 90,1%, and the negative predictive value (NPV) was 24,7%. In terms of being non-responder to induction therapy, the sensitivity was 90,1%, the specificity 25,3%, the PPV 89,8%, and the NPV was 32%. OS was shorter in those with high risk scores. Image:Summary/Conclusion: This practical and usable scoring system we developed can be supported also by new parameters.
Association Between Neighborhood Disadvantage and Fertility Among Pregnancy Planners in the US
Authors: Mary D. Willis, Olivia R. Orta, Collette Ncube, Amelia K. Wesselink, Lan N. Đoàn, Kipruto Kirwa, Renée Boynton-Jarrett, Elizabeth E. Hatch, Lauren A. Wise
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Decades of inequitable policies in the US have yielded disparities in neighborhood quality, and some studies show that living in a socioeconomically disadvantaged neighborhood is associated with worse health outcomes, including reproductive health outcomes. However, no US studies to date have directly examined the association between residence in disadvantaged neighborhoods and fertility. <h3>Objective</h3> To examine the association between residence in disadvantaged neighborhoods and fecundability, a sensitive marker of fertility with many health implications. <h3>Design, Setting, and Participants</h3> This prospective preconception cohort study used the Pregnancy Study Online, for which baseline data were collected from June 19, 2013, through April 12, 2019. The study included 6356 participants who identified as female, were 21 to 45 years of age, were attempting conception without fertility treatment, and provided a valid residential address in the contiguous US at enrollment. <h3>Exposures</h3> A standardized area deprivation index (ADI) derived at the census block group level applied to each residential address. <h3>Main Outcomes and Measures</h3> Fecundability, the per-cycle probability of conception, via questionnaires that were completed every 8 weeks for 12 months, until conception or a censoring event. Proportional probabilities models were used to estimate fecundability ratios and 95% CIs for associations between ADI and fecundability. Restricted cubic splines were also implemented to examine nonlinearity. Models were adjusted for demographic characteristics and factors associated with fertility. The study’s a priori hypothesis was that higher levels of neighborhood disadvantage would be associated with decreased fecundability. <h3>Results</h3> Among 6356 participants, 3725 pregnancies were observed for 27 427 menstrual cycles of follow-up. The mean (SD) baseline age was 30.0 (4.1) years, and most participants were non-Hispanic White (5297 [83.3%]) and nulliparous (4179 [65.7%]). Comparing the top and bottom deciles of disadvantaged neighborhood status, adjusted fecundability ratios were 0.79 (95% CI, 0.66-0.96) for national-level ADI rankings and 0.77 (95% CI, 0.65-0.92) for within-state ADI rankings. Restricted cubic splines showed some evidence of nonlinearity in the association. Associations were slightly stronger among participants with lower annual incomes (&lt;$50 000). <h3>Conclusions and Relevance</h3> In this cohort study, residence in a socioeconomically disadvantaged neighborhood was associated with moderately decreased fecundability. If confirmed in other studies, these results suggest that investments to reduce disadvantaged neighborhood status may yield positive cobenefits for fertility.
Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma
Authors: Patrick C. Lee, Susan Klaeger, Phuong M. Le, Keegan Korthauer, Jingwei Cheng, Varsha Ananthapadmanabhan, Thomas C. Frost, Jonathan D. Stevens, Alan Y.L. Wong, J. Bryan Iorgulescu, Anna Y. Tarren, Vipheaviny A. Chea, Isabel P. Carulli, Camilla K. Lemvigh, Christina B. Pedersen, Ashley K. Gartin, Siranush Sarkizova, Kyle T. Wright, Letitia W. Li, Jason Nomburg, Shuqiang Li, Teddy Huang, Xiaoxi Liu, Lucas Pomerance, Laura M. Doherty, Annie M. Apffel, Luke J. Wallace, Suzanna Rachimi, Kristen D. Felt, Jacquelyn O. Wolff, Elizabeth Witten, Wandi Zhang, Donna Neuberg, William J. Lane, Guanglan Zhang, Lars R. Olsen, Manisha Thakuria, Scott J. Rodig, Karl R. Clauser, Gabriel J. Starrett, John G. Doench, Sara J. Buhrlage, Steven A. Carr, James A. DeCaprio, Catherine J. Wu, Derin B. Keskin
Journal: Journal of Clinical Investigation (2022)

Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I-low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of 11 newly generated MCC patient-derived cell lines, we identified transcriptional suppression of several class I antigen presentation genes. To systematically identify regulators of HLA-I loss in MCC, we performed parallel, genome-scale, gain- and loss-of-function screens in a patient-derived MCPyV-positive cell line and identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as HLA-I repressors. We observed physical interaction of MYCL with the MCPyV small T viral antigen, supporting a mechanism of virally mediated HLA-I suppression. We further identify the PRC1.1 component USP7 as a pharmacologic target to restore HLA-I expression in MCC.